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Abstract

Introduction: Atrial fibrillation (AF) is the most common cardiac arrhythmia, affecting up to six million persons in the United States. The mechanism underlying AF has been extensively investigated in recent years. Reduction in oxidative capacity has been described as a contributor to several aging-related diseases including hypertension and diabetes mellitus. In vitro studies of atrial myocardium have described mitochondrial dysfunction related to reduced oxidative capacity in patients with AF. We sought to evaluate the association of plasma lactate, a marker of impaired oxidative capacity, with incident AF in a large population-based cohort.

Methods: The Atherosclerotic Risk in Communities (ARIC) study has followed 15,792 men and women from 4 US communities since 1987. We identified 11,191 participants at the 4th visit (1996-1998) without prevalent AF for whom plasma lactate levels were available. Incident AF was identified using hospital discharge codes and death certificates. The association of plasma lactate with incident AF was evaluated using Cox proportional hazards models.

Results: During a mean follow-up of 13.1 years, there were 1498 cases of incident AF. In unadjusted analysis, there was a statistically significant difference in incident AF when comparing plasma lactate by quartiles and continuously (Model 1). This association remained significant in adjusted models including age, gender, race, body-mass index, smoking, alcohol use, history of cardiovascular disease, aspirin use, statin use, total cholesterol, and glomerular filtration rate (Models 2 and 3). When adjusting for diabetes or hypertension alone, potential mediators to which reduced oxidative capacity may contribute, this association was strongly attenuated (HR per standard deviation of log(lactate) 1.04, 95% CI: 0.99, 1.10 and 1.04, 95% CI: 0.99, 1.09 respectively).

Conclusion: Plasma lactate is independently associated with incident AF, and its contribution to AF may be, at least in part, mediated by diabetes and/or hypertension.